synergism of herceptin+pertuzumab and their effect on bc stem cells IDd

[Lani]

Am J Cancer Res. 2013 Apr 3;3(2):211-220. Print 2013.
Targeting breast cancer stem cells with HER2-specific antibodies and natural killer cells.
Diessner J, Bruttel V, Becker K, Pawlik M, Stein R, Häusler S, Dietl J, Wischhusen J, Hönig A.
Source
Junior research group "tumor progression and immune escape", Interdisciplinary Center for Clinical Research (IZKF), University of Würzburg Medical School Josef-Schneider-Str. 4, 97080 Würzburg, Germany ; Department for Obstetrics and Gynecology, University of Würzburg Medical School Josef-Schneider-Str. 4, 97080 Würzburg, Germany.
Abstract
Breast cancer is the most common cancer among women worldwide. Every year, nearly 1.4 million new cases of breast cancer are diagnosed, and about 450.000 women die of the disease. Approximately 15-25% of breast cancer cases exhibit increased quantities of the trans-membrane receptor tyrosine kinase human epidermal growth factor receptor 2 (HER2) on the tumor cell surface. Previous studies showed that blockade of this HER2 proto-oncogene with the antibody trastuzumab substantially improved the overall survival of patients with this aggressive type of breast cancer. Recruitment of natural killer (NK) cells and subsequent induction of antibody-dependent cell-mediated cytotoxicity (ADCC) contributed to this beneficial effect. We hypothesized that antibody binding to HER2-positive breast cancer cells and thus ADCC might be further improved by synergistically applying two different HER2-specific antibodies, trastuzumab and pertuzumab. We found that tumor cell killing via ADCC was increased when the combination of trastuzumab, pertuzumab, and NK cells was applied to HER2-positive breast cancer cells, as compared to the extent of ADCC induced by a single antibody. Furthermore, a subset of CD44highCD24lowHER2low cells, which possessed characteristics of cancer stem cells, could be targeted more efficiently by the combination of two HER2-specific antibodies compared to the efficiency of one antibody. These in vitro results demonstrated the immunotherapeutic benefit achieved by the combined application of trastuzumab and pertuzumab. These findings are consistent with the positive results of the clinical studies, CLEOPATRA and NEOSPHERE, conducted with patients that had HER2-positive breast cancer. Compared to a single antibody treatment, the combined application of trastuzumab and pertuzumab showed a stronger ADCC effect and improved the targeting of breast cancer stem cells.
KEYWORDS:
ADCC, Trastuzumab, breast cancer, pertuzumab, tumor stem cells

PMID: 23593542 [PubMed - as supplied by publisher]

[Ellie F]

Thanks Lani
Yet another step in the right direction?
Ellie

[phil]

yet This slow FDA System will not appr. perjeta for stage iv. this is derivative science,from 20th century work on her2 , yet no appr. for stage iv this yr, maybe 2014 ?? tho they sacrifice for all research in Phase I trials. Slow FDA Costs Lives ! must be Fixed !

[KirisMum]

Perjeta IS approved as a first-line treatment for Stage IV. My daughter, recently diagnosed as stage IV, is being treated with perjeta, herceptin and taxol as a first-line approach. I believe perjeta was approved for metastatic breast cancer in February of this year. So not sure what you are referring to, Phil.

[annmask]

It was only approved as a first line of treatment, and many of us needing it have had many lines of treatment. Basically, the FDA is only approving drugs under the narrow parameters of the trial, and the trials are presented to get fastest approval, not for all patients in need. In this case, it was assumed that the combo would be most effective in a first line, and therefore the rest of us have been excluded.

[KirisMum]

I didn't realize that. How arbitrary and unfair. I can't imagine what the rationale behind limiting perjeta's availability that way could be. I'm so sorry. :-(